Breast Irradiation Tied to Cornonary Stenosis

Women undergoing radiotherapy for breast cancer are more likely to
develop blockages in the areas of their coronary arteries exposed to the
most radiation, researchers found.

The odds of developing stenosis of any severity in the mid and
distal areas, as well as the distal diagonal branch of the left anterior
descending artery, were significantly greater for women with irradiated
left-sided breast cancer compared with those who had right-sided
disease, according to Greger Nilsson, MD, of Uppsala University in
Sweden, and colleagues.

Also, radiotherapy regimens classified as high risk were associated
with increased odds of grade 3 to 5 stenosis in areas of the coronary
arteries most likely to be exposed to radiation, the researchers
reported online in the Journal of Clinical Oncology.

."Therefore, we suggest that the coronary arteries be regarded as organs at risk in radiotherapy and that every effort be made to avoid radiation dose to the coronary arteries," they wrote.

"The pathophysiology of radiation-induced heart disease involves microangiopathy of the small vessels as well as macroangiopathy of the coronary arteries, resulting in fibrosis of the myocardium, coronary artery disease, and eventually ischemic heart disease," Nilsson and colleagues explained.

To explore the relationship between radiotherapy and specific areas of the coronary arteries, the researchers examined data from a cohort of Swedish women diagnosed with breast cancer from 1970 to 2003. That information was linked to two registries of patients who underwent coronary angiography from 1990 to 2004.

The current analysis included 199 women with invasive breast cancer or ductal carcinoma in situ who underwent coronary angiography. The average age at breast cancer diagnosis was 58.2. About two-thirds of the women (62%) received radiation therapy.

The researchers defined two coronary artery hot spots that were most likely to be exposed to radiation: The proximal right coronary artery (RCA) and the mid and distal areas and distal diagonal branch of the left anterior descending artery (mdLAD+dD).

They also classified radiotherapy regimens as having high or low risk of irradiating the hot spot areas. Regimens involving the left breast/chest wall were considered to have high risk for irradiating the mdLAD+dD. Those involving the left internal mammary chain were considered to have high risk for irradiating both of the hot spots up until 1995, and after that, for the mdLAD+dD only.

Regimens involving the right internal mammary chain were considered to have high risk for irradiating the proximal RCA.

Radiotherapy for left-sided breast cancer (versus right-sided disease) was not associated with the odds of stenosis in the proximal RCA, but was associated with increased odds of stenosis of any severity in the mdLAD+dD:

OR 2.04 for grade 1 to 5 stenosis (95% CI 1.18 to 3.55)

OR 4.38 for grade 3 to 5 stenosis (95% CI 1.64 to 11.70)

OR 7.22 for grade 4 to 5 stenosis (95% CI 1.64 to 31.8)

High-risk radiotherapy regimens (versus low-risk regimens or no radiation) were associated greater odds of stenosis in the hot spot areas:

OR 1.90 for grade 3 to 5 stenosis (95% CI 1.11 to 3.24)

OR 1.87 for grade 4 to 5 stenosis (95% CI 1.14 to 3.09)

"The results lend additional support to the mounting evidence that radiotherapy can cause coronary artery disease and that there seems to be an association between the location of the radiotherapy beam and the location of the excess coronary events," according to Timothy Zagar, MD, and Lawrence Marks, MD, of the University North Carolina at Chapel Hill.

"This observation provides hope that altering the radiotherapy dose distribution will alter the risks," they wrote in an accompanying editorial. "Indeed, studies suggest that the risks of coronary artery disease are less with more modern techniques that reduce the degree of cardiac exposure."

They noted that for many patients with cancer, exposing the heart to radiation will be unavoidable.

"In these instances, we might be able to exploit knowledge of cardiac substructure anatomy to avoid the coronary arteries and other critical targets," they wrote. "Most radiation oncologists do not define the coronary arteries as structures to be avoided, but perhaps we should."

Nilsson and colleagues acknowledged some limitations of the study, including the inability to calculate the radiation dose for each woman; the lack of information on cardiovascular risk factors; and possible confounding by other treatments, or by differential referral for coronary angiography, according to type of breast cancer treatment.